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EDITORIAL
EU STANDARDS FOR TB CARE
The European Union standards for
tuberculosis care: do they need an
update?
Marieke J. van der Werf1, Andreas Sandgren1, Lia D’Ambrosio2, Francesco Blasi3
and Giovanni Battista Migliori2
Affiliations: 1European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. 2WHO
Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate,
and 3Dipartimento Fisiopatologia Medico-Chirurgica e dei Trapianti, University of Milan, IRCCS Fondazione Cà
Granda, Milan, Italy.
Correspondence: G.B. Migliori, WHO Collaborating Centre for TB and Lung Diseases, Fondazione Salvatore
Maugeri, Care and Research Institute, via Roncaccio 16, 21049, Tradate, Italy. E-mail: giovannibattista.migliori
@fsm.it
@ERSpublications
Differences between ESTC and new ISTC discussed to inform clinicians and public health officers
on best TB management http://ow.ly/tgbzt
The International Standards for Tuberculosis Care (ISTC), published for the first time in 2006 [1],
introduced a new way of looking at clinical and public health guidelines for tuberculosis (TB). The European
Respiratory Journal published an editorial explaining the ISTC, promoting the rapid uptake of the
standards [2].
While guidelines represent a long, comprehensive document containing all the details the physician might
need for managing TB, the standards are a simple set of 21 principles that guide day-to-day clinical
decisions [3, 4]. In other words, guidelines are usually available in a physician’s library while the standards
are kept on their desk in the office.
The ISTC prescribe a widely accepted level of TB care which guides all healthcare providers and clinicians,
both public and private, in achieving optimal standards in managing patients who have, or are suspected of
having, active TB [1–4].
The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society
(ERS) jointly developed a European Union (EU) adaptation of the ISTC document, known as the European
Union Standards for Tuberculosis Care (ESTC) [4]. These standards are tailored to the specific context of
the EU/European Economic Area (EEA) as follows [4, 5].
1) Although the majority of EU/EEA member states have a low incidence of TB, it is a heterogeneous setting
with some countries having a high or intermediate level of TB, with varying levels of multidrug-resistant
(MDR)-TB and TB-HIV co-infection, and some countries bordering non-EU countries with a higher TB
and MDR-TB burden.
2) TB services are fully integrated and merged within the health system in the majority of EU/EEA member
states. This presents peculiarities in allocating responsibilities for the delivery of TB care.
3) The EU/EEA member states have a long established tradition of TB control that has evolved over the past
decades. Implementation of new tools and high standards of diagnosis and care is aimed for in the EU/EEA
member states.
Received: Dec 12 2013
|
Accepted after revision: Jan 09 2014
Conflict of interest: Disclosures can be found alongside the online version of this article at www.erj.ersjournals.com
Eur Respir J 2014; 43: 933–942 | DOI: 10.1183/09031936.00216613
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4) Several EU/EEA member states are pursuing TB elimination, sharing a common platform (based on the
Wolfheze documents [6] and the Framework Action Plan to Fight TB in the EU [7]) with the ECDC and
World Health Organization (WHO)-coordinated TB surveillance network and system [6–9].
The standards are designed as a living document that will be revised as technology, resources and
circumstances change. Also, they complement existing national or international guidelines, being consistent
with the WHO definitions and recommendations [5]. The ISTC were revised in 2009, while a new third
edition has recently been presented to commemorate the 2014 World TB Day [3]. This prompted the ECDC
and the ERS to compare the third edition of the ISTC and the ESTC to see what the differences are and to
evaluate if a revision of the ESTC is necessary.
The core ECDC and ERS experts who coordinated the effort of the expert group developing the ESTC made
a careful comparison of the new ISTC and ESTC standards (table 1), underlining the content that was not
shared by both documents and summarising the differences. This will allow clinicians and public health
officers to rapidly capture the innovative elements included in the third edition of the ISTC and understand
to what extent they can be applied in the EU/EEA setting.
In terms of structure, the ESTC (consistent with the second edition of the ISTC [16]) contained 21
standards organised into four sections: 1) standards for diagnosis; 2) standards for treatment; 3) standards
for addressing HIV infection and other comorbid conditions; and 4) standards for public health.
A new standard has been included in the third edition of the ISTC [3], to make clinicians aware that specific
risk groups exist and that TB has a higher prevalence in these risk groups than in the general population.
This issue is tackled by the ESTC in standards 1 and 4 (table 1).
No relevant differences were found between the ESTC and ISTC in standards 9, 13, 14, 17, 19, 20 and 21.
In standard 1, the ESTC take into account the variability of signs and symptoms TB presents with, while the
ISTC make reference to chronic cough as the global ‘‘pivotal’’ symptom traditionally allowing investigation
of a patient for TB. It seems adequate to describe the reality of the EU setting in the ESTC where chronic
cough is more related to smoking and other lung diseases.
In standard 2, while the ISTC recommend Xpert MTB/RIF as the first choice for diagnosis (consistent with
the present WHO policy to promote the wide peripheral use of the test [10–12]), the ESTC mention rapid
testing for the identification of rifampicin and isoniazid resistance using validated tools. This makes sense in
the EU, given the focus is on quality-assured culture-based methods and easy access to drug susceptibility
testing (DST). The ESTC does not yet include a negative recommendation on blood-based serological
tests since this WHO recommendation was published after the launch of the ESTC [13]. The WHO
recommendation is for the use of interferon-c release assays (IGRAs) in low- and middle-income countries
[14]. Specific guidance on the use of IGRAs in the EU is provided by the ECDC [17–19]. In the perspective
of TB elimination, IGRAs might gain additional interest in the diagnosis of TB infection.
Similarly, in standard 3 the ESTC advocate the use of culture and DST in extrapulmonary TB, while the
ISTC consistently recommend the use of Xpert MTB/RIF.
In standard 5, the ESTC provide guidance on how to diagnose culture-negative TB, while the ISTC focus on
smear-negative TB. For diagnosing culture-negative TB, a trial of broad-spectrum antimicrobials may be
used according to the ESTC standard, such trial regimens should not include fluoroquinolones. The ESTC
specifically recommend expedited investigation of immunocompromised patients, who represent a priority
in the EU setting.
Standard 6 of the ISTC indicates that along with sputum smear microscopy and culture, the Xpert MTB/RIF
test can also be used for bacterial confirmation of TB in children. The corresponding ESTC standard
provides more details on how to diagnose TB in children.
In standard 7, the ESTC underline the need for the treating physician to collaborate with the local public
health and/or community health services to perform a contact investigation [20].
Standard 8, apart from the different wording (internationally recommended treatment regimens in ESTC
versus WHO recommended regimens in ISTC), is consistent in the two documents. The ESTC recommends
the use of fixed-dose combinations.
In standard 10, the ISTC is more prescriptive on what test to use for DST when the sputum is still positive at
3 months, i.e. Xpert MTB/RIF should be used.
In standard 11, the ISTC is more restrictive in recommending DST. Instead of recommending it for all TB
patients, as in the ESTC, the ISTC recommend DST for previously treated patients, patients who remain
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4. For all patients (including children) suspected of having
extrapulmonary TB, appropriate specimens from the
suspected sites of involvement should be obtained for
microbiological and histopathological examination. An Xpert
MTB/RIF test is recommended as the preferred initial
microbiological test for suspected tuberculous meningitis
because of the need for a rapid diagnosis
3. For all patients (adults, adolescents and children)
suspected of having extrapulmonary TB, appropriate
specimens from the suspected sites of involvement
should be obtained for microscopy, culture, DST and
histopathological examination in a quality-assured
laboratory. In countries, settings or populations in which
MDR-TB is suspected in a patient, rapid testing for the
identification of rifampicin and isoniazid resistance in a
quality-assured laboratory could be performed
4. All persons with chest radiographic findings suggestive of
pulmonary TB should have sputum specimens submitted
for microscopic examination, culture and DST in a
quality-assured laboratory. In countries, settings or
populations in which MDR-TB is suspected in a patient,
rapid testing for the identification of rifampicin resistance
and, when possible, isoniazid resistance in a
quality-assured laboratory should be performed
Combined with standard 2
3. All patients (including children) who are suspected of having
pulmonary TB and who are capable of producing sputum
should have at least two sputum specimens submitted for
smear microscopy or a single sputum specimen for Xpert
MTB/RIF testing in a quality-assured laboratory. Patients at
risk for drug resistance, who have HIV risk or who are
seriously ill should have Xpert MTB/RIF performed as the
initial diagnostic test. Blood-based serological tests and
IGRA should not be used for diagnosis of active TB
2. All patients (including children) with unexplained cough
lasting o2 weeks or with unexplained findings suggestive of
TB on chest radiographs should be evaluated for TB
1. To ensure early diagnosis, providers must be aware of
individual and group risk factors for TB and perform prompt
clinical evaluations and appropriate diagnostic testing for
persons with symptoms and findings consistent with TB
ISTC [3]
2. All patients (adults, adolescents and children who are
capable of producing sputum) suspected of having
pulmonary TB should have at least two sputum specimens
submitted for microscopic examination, culture and DST
in a quality-assured laboratory. When possible, at least
one early morning specimen should be obtained. In
countries, settings or populations in which MDR-TB is
suspected in a patient, rapid testing for the identification
of rifampicin and isoniazid resistance, using validated
tools in a quality-assured laboratory, should be performed
Standards for TB diagnosis
1. All persons presenting with signs, symptoms, history or
risk factors compatible with TB should be evaluated for
pulmonary and/or extrapulmonary TB
ESTC [4]
The ISTC standard puts focus on the signs and symptoms
of cough and unexplained findings suggestive of TB on
chest radiographs, while according to the ESTC
persons with any signs or symptoms compatible with
TB should be evaluated. The ESTC standard specifically
mentions individual risk factors for TB. This is taken
into account in the new ISTC standard
WHO recommendations for Xpert MTB/RIF [10–12] are
included in the ISTC standard whereas the ESTC
standard mentions rapid testing for the identification of
rifampicin and isoniazid resistance, using validated
tools
The ESTC standard recommends DST for all patients
The ESTC standard puts more focus on the use of quality
assured culture-based methods as these are more
broadly available in the EU
The 2011 WHO policy statement [13] against the use of
blood-based serological tests and the 2011 WHO policy
statement against the use of IGRAs [14] in low- and
middle-income countries have been included in the
ISTC
The ISTC standard includes a specific recommendation
for using the Xpert MTB/RIF test as the preferred initial
microbiological test for suspected TB meningitis
because of the need for a rapid diagnosis
The ESTC emphasises culture confirmation and rapid
testing of MDR-TB for all extrapulmonary TB cases, but
does not specify which type of rapid molecular testing
to use
New standard included in ISTC
Differences
TABLE 1 Differences between the European Union Standards for Tuberculosis care (ESTC) and the third edition of the International Standards for Tuberculosis
Care (ISTC)
EU STANDARDS FOR TB CARE | M.J. VAN DER WERF ET AL.
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5. The diagnosis of culture-negative pulmonary TB should
be based on the following criteria: all bacteriological tests
are negative (including direct sputum smear examinations,
cultures and rapid molecular testing); chest radiographic
findings are compatible with TB; there is a lack of response
to a trial of broad-spectrum antimicrobial agents (because
fluoroquinolones are active against Mycobacterium
tuberculosis complex and, thus, may cause transient
improvement in persons with TB, they should be avoided).
In persons who are seriously ill or have known or suspected
HIV infection or have any immunocompromising conditions,
the diagnostic evaluation should be expedited and, if clinical
evidence strongly suggests TB, a course of anti-TB
treatment should be initiated
6. In all children suspected of having intrathoracic TB (i.e.
pulmonary, pleural and mediastinal or hilar lymph node),
bacteriological confirmation should be sought through
examination of appropriate biological samples (expectoration
or induced sputum, bronchial secretions, pleural fluid or
gastric washings) for smear microscopy, culture and DST in a
quality-assured laboratory. In the event of negative
bacteriological results, a diagnosis of TB should be based on
the presence of abnormalities consistent with TB on chest
radiography or other imaging, a history of exposure to an
infectious case, evidence of TB infection (positive TST and/or
IGRA) and clinical findings suggestive of TB. For children
suspected of having extrapulmonary TB, appropriate
specimens from the suspected sites of involvement
should be obtained for microscopy, culture, DST and
histopathological examination
Standards for TB treatment
7. Any practitioner treating a patient for TB is assuming an
important public health responsibility to prevent ongoing
transmission of the infection and the development of drug
resistance. To fulfil this responsibility the practitioner
must not only prescribe an appropriate regimen, but also
utilise local public and/or community health services,
agencies and resources when necessary, to perform
contact investigation, to assess the adherence of the
patient and to address poor adherence when it occurs
ESTC [4]
TABLE 1 Continued
Differences
The main difference is that the ESTC standard uses the
culture-based case definition and the ISTC standard
uses the sputum smear status. The ISTC includes the
use of Xpert MTB/RIF as a diagnostic test for patients
with pulmonary TB and negative sputum smears. The
ESTC does not specify which type of rapid molecular
test should be used
A trial of broad-spectrum antimicrobial agents is
recommended by the ESTC
A specific recommendation for expedited investigation of
immunocompromised patients is included in the ESTC
standard
The ISTC standard indicates that as well as smear
microscopy and culture, the Xpert MTB/RIF test can be
used for bacterial confirmation of TB in children.
The ESTC standard provides more details on how to
diagnose TB in children
The ESTC standard specifically mentions the obligation of
the practitioner treating a TB patient to collaborate with
the local public and/or community health services to
perform contact investigation
ISTC [3]
5. In patients suspected of having pulmonary TB whose
sputum smears are negative, Xpert MTB/RIF and/or sputum
cultures should be performed. Among smear and Xpert
MTB/RIF negative persons with clinical evidence strongly
suggestive of TB, anti-TB treatment should be initiated after
collection of specimens for culture examination
6. In all children suspected of having intrathoracic TB (i.e.
pulmonary, pleural and mediastinal or hilar lymph node),
bacteriological confirmation should be sought through
examination of respiratory secretions (expectorated
sputum, induced sputum or gastric lavage) for smear
microscopy, Xpert MTB/RIF test and/or culture
7. To fulfil their health responsibility, as well as their
responsibility to the individual patient, the provider must
prescribe an appropriate treatment regimen, monitor
adherence to the regimen and, when necessary, address
factors leading to interruption or discontinuation of
treatment. Fulfilling these responsibilities will probably
require coordination with local public health services
and/or other local services
EU STANDARDS FOR TB CARE | M.J. VAN DER WERF ET AL.
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8. All patients (including those with HIV infection) who have
not been previously treated and without any risk factors
for drug resistance should receive an internationally
accepted first-line treatment regimen using drugs of
known bioavailability. The initial phase should consist of
2 months of isoniazid, rifampicin, pyrazinamide and
ethambutol. The continuation phase should consist of
isoniazid and rifampicin given for 4 months (2HRZE/4HR).
The doses of anti-TB drugs used should conform to
international recommendations. Fixed dose combinations
of two (isoniazid and rifampicin), three (isoniazid,
rifampicin and pyrazinamide) and four (isoniazid,
rifampicin, pyrazinamide and ethambutol) drugs are
highly recommended
9. To assess and foster adherence, a patient-centred
approach to administration of drug treatment, based on
the patient’s needs and mutual respect between the
patient and the provider, should be developed for all
patients
Supervision and support should be individualised and should
draw on the full range of recommended interventions and
available support services, including patient counselling and
education. A central element of the patient-centred
strategy is the use of measures to assess and promote
adherence to the treatment regimen and to address poor
adherence when it occurs. These measures should be
tailored to the individual patient’s circumstances, based
on a detailed anamnesis of the patient’s clinical and social
history, and be mutually acceptable to the patient and the
provider. Such measures may include direct observation
of medication ingestion (directly observed treatment) and
identification and training of a treatment supporter (for TB
and, if appropriate, HIV infection) who is acceptable and
accountable to the patient and to the health system.
Appropriate incentives and enablers, including financial,
social and psychosocial supports, may also serve to
enhance treatment adherence
ESTC [4]
TABLE 1 Continued
The ISTC standard specifically mentions that patients
should be treated with a WHO-approved first-line
treatment regimen whereas the ESTC standard
mentions an internationally accepted first-line
treatment regimen
The ESTC standard promotes the use of fixed dose
combinations
There are no relevant differences between the ESTC
and the ISTC standards
The ESTC standard provides more details about how
and what supervision and support should be provided
9. A patient-centred approach to treatment should be
developed for all patients in order to promote adherence,
improve quality of life and relieve suffering. This approach
should be based on the patient’s needs and mutual respect
between the patient and the provider
Differences
8. All patients who have not been treated previously and do not
have other risk factors for drug resistance should receive a
WHO-approved first-line treatment regimen using
quality-assured drugs. The initial phase should consist of
2 months of isoniazid, rifampicin, pyrazinamide nd
ethambutol. The continuation phase should consist of
isoniazid and rifampicin given for 4 months. The doses of
anti-TB drugs used should conform to WHO recommendations.
Ethambutol may be omitted in children who are HIV negative
and who have non-cavitary disease
ISTC [3]
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12. Patients with, or highly likely to have, TB caused by
drug-resistant (especially MDR-/XDR-TB) organisms
should be treated with specialised regimens containing
second-line anti-TB drugs. The regimen chosen may be
standardised or based on suspected or confirmed drug
susceptibility patterns. At least four drugs to which the
organisms are known or presumed to be susceptible to,
including an injectable agent and pyrazinamide, should be
used. Treatment should be given for at least 20 months,
the recommended intensive phase of treatment being
8 months (instead of 6 months as in previous
recommendations)
11. An assessment of the likelihood of drug resistance,
based on history of prior treatment, exposure to a possible
source case having drug-resistant organisms and the
community prevalence of drug resistance, should be
obtained for all patients. Rapid testing, including rapid
rifampicin and isoniazid resistance testing should be
performed for all patients suspected of resistance as
defined in standards 2 and 8. Furthermore, patient
counselling and education should begin immediately for
all TB patients, in order to minimise the potential for
transmission. Infection control measures appropriate to
the setting should be applied as recommended in ESTC
public health standard 20
10. Response to therapy in patients with pulmonary TB
should be monitored by follow-up smear microscopy and
culture at the time of completion of the initial phase of
treatment (2 months for drug-susceptible TB). If the
sputum smear and culture are positive at completion of
the initial phase, sputum smears should be examined
again at 3 months and, if positive, DST should be
performed. In patients with extrapulmonary TB and in
children unable to produce sputum, the response to
treatment is assessed clinically
ESTC [4]
TABLE 1 Continued
The ISTC standard specifically mentions that patients
diagnosed by a rapid molecular test should be
monitored
The ISTC standard mentions that if sputum is still positive
at 3 months a rapid molecular DST (Line-probe assays
or Xpert MTB/RIF) or culture with DST should be
performed. The ESTC standard does not specify the test
to be used for DST
10. Response to treatment in patients with pulmonary TB
(including those with TB diagnosed by a rapid molecular
test) hould be monitored by follow-up sputum microscopy at
the time of completion of the initial phase of treatment
(2 months). If the sputum smear is positive at completion of
the initial phase, sputum microscopy should be performed
again at 3 months and, if positive, rapid molecular drug
sensitivity testing (Line-probe assays or Xpert MTB/RIF) or
culture with DST should be performed. In patients with
extrapulmonary TB and in children, the response to
treatment is best assessed clinically
11. An assessment of the likelihood of drug resistance, based
on history of prior treatment, exposure to a possible source
case having drug-resistant organisms, and the ommunity
prevalence of drug resistance (if known), should be obtained
for all patients. DST should be performed at the start of
therapy for all previously treated patients. Patients who
remain sputum smear positive at completion of 3 months of
treatment and patients in whom treatment has failed, have
been lost to follow-up, or relapsed following one or more
courses of treatment should always be assessed for drug
resistance. For patients in whom drug resistance is considered
to be likely, an Xpert MTB/RIF test should be the initial
diagnostic test. Line-probe assay or culture and testing for
susceptibility to at least isoniazid and rifampicin should be
performed promptly if rifamycin resistance is detected. Patient
counselling and education, as well as an empiric second-line
treatment regimen, should begin immediately to minimise the
potential for transmission. Infection control measures
appropriate to the setting should be applied
12. Patients with, or highly likely to have, TB caused by
drug-resistant (especially MDR-/XDR-TB) organisms should
be treated with specialised regimens containing
quality-assured second-line anti-TB drugs. The doses of
anti-TB drugs should conform to WHO recommendations.
The regimen chosen may be standardised or based on
suspected or confirmed drug susceptibility patterns. At least
pyrazinamide and four drugs to which the organisms are
known or presumed to be susceptible, including an injectable
agent, should be used in an 8 month intensive phase and at least
three drugs to which the organisms are known or presumed
to be susceptible should be used in the continuation phase.
Treatment should be given for at least 18–24 months beyond
ulture conversion. Patient-centred measures, including
observation of treatment, are required to ensure adherence.
Consultation with a specialist experienced in treatment of
patients with MDR-/XDR-TB should be obtained
The ISTC standard recommends that the doses of the
anti-TB drugs should conform to WHO
recommendations
The ISTC standard specifies that the continuation phase
needs to contain at least three drugs to which the
organisms are known or presumed to be susceptible
The ISTC standard is more restrictive in recommending
DST. Instead of recommending it for all TB patients
(ESTC) it recommends DST for previously treated
patients, patients who remain sputum smear positive at
completion of 3 months of treatment and patients in
whom treatment has failed, who have been lost to
follow-up, or who relapsed following one or more
courses of treatment
The ESTC standard recommends rapid testing, whereas
the ISTC standard recommends using the Xpert MTB/
RIF test for patients in whom drug resistance is
considered to be likely, followed by a Line-probe assay
if rifamycin resistance is detected. A note to the ESTC
standard stresses that rapid molecular testing does not
rule out the requirement to perform culture DST to
confirm results
Differences
ISTC [3]
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16. Persons with HIV infection who, after careful evaluation, do
not have active TB should be treated for presumed LTBI with
isoniazid for at least 6 months
17. All providers should conduct a thorough assessment for
comorbid conditions and other factors that could affect TB
treatment response or outcome and identify additional
services that would support an optimal outcome for each
patient. These services should be incorporated into an
individualised plan of care that includes assessment of and
referrals for treatment of other illnesses. Particular
attention should be paid to diseases or conditions known to
affect treatment outcome, e.g. diabetes mellitus, drug and
alcohol abuse, under nutrition and tobacco smoking.
Referrals to other psychosocial support services or to such
services as antenatal or well-baby care should also be
provided
17. All providers should conduct a thorough assessment of
conditions that could affect TB treatment response or
outcome. At the time the case management plan is
developed, the provider should identify additional services
that would support an optimal outcome for each patient
and incorporate these services into an individualised plan
of care. This plan should include assessment of and
referrals for treatment of other illnesses with particular
attention to those known to affect treatment outcome, for
instance care for diabetes mellitus, drug and alcohol
treatment programmes, tobacco smoking cessation
programmes and other psychosocial support services,
or to such services as antenatal or well-baby care
There are no relevant differences between the ESTC and
the ISTC standards
14. HIV testing and counselling should be conducted for all
patients with, or suspected of having, TB unless there is a
confirmed negative test within the previous 2 months.
Because of the close relationship of TB and HIV infection,
integrated approaches to prevention, diagnosis and
treatment of both TB and HIV infection are recommended in
areas with high HIV prevalence. HIV testing is of special
importance as part of routine management of all patients in
areas with a high prevalence of HIV infection in the general
population, in patients with symptoms and/or signs of
HIV-related conditions, and in patients having a history
suggestive of high risk of HIV exposure
15. In persons with HIV infection and TB who have profound
immunosuppression (CD4 counts ,50 cells?mm-3), ART
should be initiated within 2 weeks of beginning treatment
for TB unless tuberculous meningitis is present. For all
other patients with HIV and TB, regardless of CD4 counts,
ART should be initiated within 8 weeks of beginning
treatment for TB. Patients with TB and HIV infection should
also receive cotrimoxazole as prophylaxis for other
infections
The ISTC standard includes the 2013WHO
recommendation that ART should be initiated within
2 weeks of beginning treatment for TB in persons with
profound immunosuppression unless tuberculous
meningitis is present [15]. For all other patients with
HIV and TB, regardless of CD4 counts, ART should be
initiated within 8 weeks of beginning treatment for TB
The ESTC standard does not provide recommendations
for patients with HIV infection, while the ISTC standard
does, i.e. co-infected patients should receive
cotrimoxazole as prophylaxis for other infections
The ISTC standard recommends that all persons with HIV
infection and without active TB, independent of having a
positive test for LTBI, are treated for presumed LTBI
whereas the ESTC standard only recommends
preventive treatment for those with a positive LTBI test
or who are highly probable to have LTBI
There are no relevant differences between the ESTC and
the ISTC standards
There are no relevant differences between the ESTC and
the ISTC standards
Differences
13. An accessible, systematically maintained record of all
medications given, bacteriologic response, outcomes and
adverse reactions should be maintained for all patients
ISTC [3]
16. Persons with HIV infection who, after careful evaluation,
have a positive test for presumed LTBI with M. tuberculosis
(TST and/or IGRAs) but do not have active TB should be
treated with isoniazid for 6–9 months or any new regimen
for which evidence becomes available
15. All patients with TB and HIV infection should be
evaluated to determine if ART is indicated during the
course of treatment for TB, according to the severity of
their immunodeficiency. Appropriate arrangements for
access to antiretroviral drugs should be made for patients
who meet indications for treatment. However, initiation of
treatment for TB should not be delayed and the
antiretroviral treatment prescribed as soon as possible
based on evidence
13. A written record of all medications given, bacteriological
response and adverse reactions should be maintained for
all patients
Standards for addressing HIV infection and comorbidity
conditions
14. HIV testing and counselling should be recommended to
all patients with, or suspected of having, TB. Testing is of
special importance as part of the routine management of
all patients in areas with a high prevalence of HIV infection
in the general population and in patients with symptoms
and/or signs of HIV-related conditions. Because of the
close relationship between TB and HIV infection,
integrated approaches to prevention and treatment of both
infections are recommended
ESTC [4]
TABLE 1 Continued
EU STANDARDS FOR TB CARE | M.J. VAN DER WERF ET AL.
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There are no relevant differences between the ESTC and
the ISTC standards
19. Children ,5 years of age and persons of any age with HIV
infection who are close contacts of patient person with
infectious TB and who, after careful evaluation, do not have
active TB should be treated for presumed LTBI with
isoniazid for at least 6 months
20. Each healthcare facility caring for patients who have, or
are suspected of having, infectious TB should develop and
implement an appropriate TB infection control plan to
minimise possible transmission of M. tuberculosis to
patients and healthcare workers
21. All providers must report both new and re-treatment TB
cases and their treatment outcomes to local public health
authorities, in conformance with applicable legal
requirements and policies
There are no relevant differences between the ESTC and
the ISTC standards
There are no relevant differences between the ESTC and
the ISTC standards
The ESTC standard does not provide a list of priority
contacts for evaluation, instead it provides the
determinants of TB transmission and susceptibility of a
contact that should be assessed
Differences
18. All providers should ensure that persons who are in close
contact with patients who have infectious TB are evaluated
and managed in line with international recommendations.
The highest priority contacts for evaluation are persons with
symptoms suggestive of TB, children aged ,5 years,
contacts with known or suspected immunocompromised
states (particularly HIV infection), and contacts of patients
with MDR-/XDR-TB
ISTC [3]
TB: tuberculosis; DST: drug susceptibility testing; MDR: multidrug resistant; IGRA: interferon-c release assay; WHO: World Health Organization; H: isoniazid; R: rifampicin; Z: pyrazinamide;
E: ethambuthol; EU: European Union; TST: tuberculin skin test; XDR: extensively-drug resistant; ART: antiretroviral therapy; LTBI: latent TB infection. Xpert MTB/RIF test is manufactured by
Cepheid (Sunnyvale, CA, USA).
21. All providers must report both new and retreatment TB
cases and their treatment outcomes to local public health
authorities, in conformance with applicable legal
requirements and policies
Standards for public health and TB prevention
18. All providers of care for patients with TB should ensure
that persons who are in close contact with patients who
have infectious TB (e.g. in families, congregate settings
like migrants shelters, schools and prisons), are
evaluated and managed in line with international
recommendations. The risk of TB transmission depends
on the concentration of the mycobacteria in the air, the
duration of the contact and the susceptibility of the contact
to infection and disease. The determination of priorities
for contact investigation is based on the likelihood that a
contact has undiagnosed TB, is at high risk of having been
infected by the index case, is at high risk of developing TB
if infected, and is at risk of having severe TB if the disease
develops
19. Children ,5 years of age and persons of any age with
HIV infection who are close contacts of an infectious index
patient and who, after careful evaluation, do not have
active TB should be treated for presumed LTBI with
isoniazid
20. Each healthcare facility caring for patients who have, or
are suspected of having, infectious TB should develop and
implement an appropriate TB infection control plan
ESTC [4]
TABLE 1 Continued
EU STANDARDS FOR TB CARE | M.J. VAN DER WERF ET AL.
DOI: 10.1183/09031936.00216613
EU STANDARDS FOR TB CARE | M.J. VAN DER WERF ET AL.
sputum smear positive at completion of 3 months of treatment, and patients in whom treatment has failed,
patients lost to follow-up, or patients who relapsed following one or more treatment courses.
In standard 12 the recommendations are quite similar. The ESTC contain an EU-adapted supplement
focusing on the need to treat MDR-TB cases in specialised settings with individualised and DST-based
regimens, and under the guidance of a panel of experts [21–24].
The ISTC standard 15 includes the recent WHO recommendations to initiate antiretroviral treatment
within 2 weeks of beginning TB treatment in HIV-infected individuals with profound immunosuppression
or within 8 weeks for all others [15]. The ESTC specifies that patients with TB and HIV should be evaluated
to determine if antiretroviral therapy is indicated.
The main difference between the ISTC and the ESTC in standard 16 is that the ISTC recommend treatment
of latent TB infection for all HIV-infected persons who do not have active TB whereas the ESTC only
recommend it for those either infected or likely to be infected by Mycobacterium tuberculosis.
In standard 18 the ISTC provides a specific list of priority contacts for contact evaluation, whereas the ESTC
states which determinants of TB transmission and susceptibility of a contact should be evaluated.
The analysis of the differences between the two documents (table 1) shows the consistency of their
recommendations given the different setting (EU versus global) in which they are applied.
As new evidence is rapidly growing, a revision of the ESTC will be appropriate in about 2 years. The critical
elements that will require modification will be represented, in our opinion, by the following factors: 1) the
WHO post-2015 strategy, which will emphasise elimination and will pose new targets and milestones;
2) the progressive implementation of the ECDC elimination framework vis-à-vis the evidence on how the
interventions necessary to reach elimination are applied in the EU [6, 25, 26]; and 3) the introduction of
new drugs and new regimens (potentially involving delamanid, bedaquiline and PA-824) to treat MDR-TB,
but also potentially drug-susceptible TB and latent TB infection [27–30].
We hope that the comparative analysis of the two documents will further contribute to help clinicians in
making the correct diagnosis and in the undertaking the correct treatment and public health actions, to
ensure the best management of TB and MDR-TB cases.
Acknowledgements
We wish to thank R. Centis (WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and
Research Institute, Tradate, Italy) for her suggestions and technical support, and P. Hopewell and F. Du Melle (American
Thoracic Society, New York, NY, USA) for ensuring consistency of this document with the final version of the
International Standards for Tuberculosis Care.
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